DETERMINATION OF P-TRIFLUOROMETHYLPHENOL, A METABOLITE OF FLUOXETINE,IN TISSUES AND BODY-FLUIDS USING AN ELECTRON-CAPTURE GAS-CHROMATOGRAPHIC PROCEDURE

An electron-capture gas chromatographic procedure was developed for th e analysis of p-trifluoromethylphenol, an O-dealkylated metabolite of fluoxetine, in biological samples. A basic extraction of the biologica l sample was employed, followed by derivatization with pentafluorobenz enesulfonyl chloride. The internal standard, 2,4-dichlorophenol, was a dded to all samples used in the procedure to aid in quantitation. The practical limit of detection (signal-to-noise ratio>3) for p-trifluoro methylphenol was <5 ng/ml in human plasma samples, <10 ng/g of rat bra in tissue, <25 ng/g of rat liver tissue and <25 ng/ml in human and rat urine samples. In the rat, the levels of free p-trifluoromethylphenol in the liver were 10-fold higher than those in the brain, and a subst antial amount was excreted in the urine. Human urine samples contained levels of free p-trifluoromethylphenol approximately 30-fold higher t han those found in human plasma samples. The procedure described is us eful for the detection and quantitation of free p-trifluoromethylpheno l in humans and rats treated with fluoxetine. (C) 1997 Elsevier Scienc e B.V.